HCV CARE

Hepatitis C Virus Infection Guideline Committee, December 2017

All regimens listed in this guideline were available as of July 1, 2017

These recommendations on treatment of chronic HCV were developed by the New York State (NYS) Department of Health (DOH) Hepatitis C Virus Infection Guideline Committee to guide primary care providers and other clinicians in NYS in treating patients with chronic HCV infection.

HIV/HCV coinfection: Treatment of chronic HCV infection in patients with HIV infection requires attention to drug-drug interactions between DAAs and antiretrovirals (ARVs) and to a few other HIV-specific treatment issues (see Treatment for Patients with HIV and HCV Coinfection section of this guideline). Otherwise, clinicians should follow the recommendations below for treatment of patients with HCV monoinfection and consult care providers experienced in HCV treatment and in HIV treatment as needed.

KEY POINTS: CHOOSING AN ANTI-HCV TREATMENT REGIMEN
  • Treatment regimen recommendations are organized according to HCV genotype and subtype, the presence or absence of compensated cirrhosis, and HCV treatment history.
  • The recommended regimens within each list are in alphabetical order, not in order of preference.
  • No single regimen is recommended over another within each list of options; data on direct comparisons of treatment regimens have not been published.
  • The choice of regimen should be based on individual pretreatment assessment findings, the general considerations detailed above, and insurance coverage.
  • The regimens recommended for retreatment are for patients who have been treated previously with DAAs or pegylated interferon (PEG-IFN) plus ribavirin (RBV).

Recommended oral direct-acting antiviral drugs and drug regimens are listed in Table 7, below. All regimens listed in drug regimen tables for all HCV genotypes refer to oral medications.

Table 7. Recommended Oral Direct-Acting Antiviral Drugs and Drug Regimens
Drug/Combination Trade Name
Elbasvir/grazoprevir* Zepatier
Glecaprevir/pibrentasvir Mavyret
Ledipasvir/sofosbuvir* Harvoni
Paritaprevir/ritonavir/ombitasvir Technivie
Paritaprevir/ritonavir/ombitasvir/dasabuvir* (PrOD) Viekira XR
Sofosbuvir Sovaldi
Sofosbuvir/velpatasvir* Epclusa
Sofosbuvir/velpatasvir/voxilaprevir Vosevi
*These drugs are co-formulated (indicated by the “/”).

 

Genotype 1a

Hepatitis C Virus Infection Guideline Committee, December 2017

RECOMMENDATIONS
  • Based on the results of the pretreatment assessment, clinicians should choose from among the treatment regimens for patients with hepatitis C virus (HCV) genotype 1a listed in tables 8 through 11, below.
  • Clinicians should test for the presence of NS5A resistance-associated variants (RAVs) before starting therapy with elbasvir/grazoprevir in all patients with HCV genotype 1a infection. (AIII)
  • If a regimen with weight-based ribavirin (RBV) is chosen, clinicians should dose as follows: (AI)
    • <75 kg: RBV 400 mg once daily + 600 mg once daily (total daily dose: 1000 mg)
    • ≥75 kg: RBV 600 mg twice daily (total daily dose: 1200 mg)

The regimens listed in tables 8 through 11, below, are recommended for patients with HCV genotype 1a. All drugs in the recommended regimens below are oral medications. Multiple factors influence the choice of regimen, including, but not limited to, the patient’s treatment status (naive or previous HCV treatment failure), the presence of cirrhosis, preferences, and all previously noted considerations.

Drug names: Use of a “/” between two drug names indicates a co-formulated tablet. Use of the word “plus” indicates two separate drugs.

Rating of regimens: All regimen choices listed below are rated AI (strong recommendation, with high quality evidence from at least 1 randomized trial with clinical outcomes and/or validated laboratory endpoints) except where indicated. 

Table 8.  Genotype 1a • Treatment-naive • No cirrhosis

Choose 1 of the following regimens: (AI)

Duration

Glecaprevir 300 mg/pibrentasvir 120 mg once daily [1,2]
(GLE/PIB; Mavyret)

8 weeks

Paritaprevir 150 mg/ritonavir 100 mg/ombitasvir 25 mg/dasabuvir 600 mg  once daily plus weight-based ribavirin twice daily [3,4]
(PTV/RTV/OBV/DSV; PrOD; Viekira XR plus RBV; Copegus) 

12 weeks

Sofosbuvir 400 mg/velpatasvir 100 mg once daily [5-7]
(SOF/VEL; Epclusa)

12 weeks

Without baseline NS5A polymorphisms: Elbasvir 50 mg/grazoprevir 100 mg once daily [6-8]
(ELB/GRZ; Zepatier)

12 weeks
With baseline NS5A polymorphisms: Elbasvir 50 mg/grazoprevir 100 mg once daily plus weight-based ribavirin twice daily [9]
(ELB/GRZ; Zepatier plu RBV; Copegus)
16 weeks

For patients who are non-black, HIV-uninfected, and have HCV RNA <6 million copies/mL (AII): Ledipasvir 90 mg/sofosbuvir 400 mg once daily [10-13]
(LED/SOF; Harvoni)

8 weeks

For patients who are black, HIV-infected, or have HCV RNA ≥6 million copies/mL: Ledipasvir 90 mg/sofosbuvir 400 mg once daily [10-13]
(LED/SOF; Harvoni)

12 weeks

 

Table 9. Genotype 1a • Treatment-naive • Compensated cirrhosis

Choose 1 of the following regimens (AI):

Duration

Glecaprevir 300 mg/pibrentasvir 120 mg once daily [2,14]
(GLE/PIB; Mavyret)

12 weeks

Ledipasvir 90 mg/sofosbuvir 400 mg once daily [15,16]
(LED/SOF; Harvoni)

12 weeks

Paritaprevir 150 mg/ritonavir 100 mg/ombitasvir 25 mg/dasabuvir 600 mg once daily plus weight-based ribavirin twice daily [17]
(PTV/RTV/OBV/DSV; PrOD; Viekira XR plus RBV; Copegus)

12 weeks

Sofosbuvir 400 mg/velpatasvir 100 mg once daily [5]
(SOF/VEL; Epclusa)

12 weeks

Without baseline NS5A polymorphisms: Elbasvir 50 mg/grazoprevir 100 mg once daily [6,8]
(ELB/GRZ; Zepatier)

12 weeks
With baseline NS5A polymorphisms: Elbasvir 50 mg/grazoprevir 100 mg once daily plus weight-based ribavirin twice daily [9]
(ELB/GRZ; Zepatier plus RBV; Copegus)
16 weeks

 

Table 10. Genotype 1a • Prior failure with PEG-IFN* • No cirrhosis 

Choose 1 of the following regimens for retreatment (AI):

Duration

Glecaprevir 300 mg/pibrentasvir 120 mg once daily [1,2]
(GLE/PIB; Mavyret)

8 weeks

Ledipasvir 90 mg/sofosbuvir 400 mg once daily [18]
(LED/SOF; Harvoni)

12 weeks

Paritaprevir 150 mg/ritonavir 100 mg/ombitasvir 25 mg/dasabuvir 600 mg  once daily plus weight-based ribavirin twice daily [19]
(PTV/RTV/OBV/DSV; PrOD; Viekira XR plus RBV; Copegus)

12 weeks

Sofosbuvir 400 mg/velpatasvir 100 mg once daily [5]
(SOF/VEL; Epclusa)

12 weeks

Without baseline NS5A polymorphisms: Elbasvir 50 mg/grazoprevir 100 mg once daily [20]
(ELB/GRZ; Zepatier)

12 weeks
With baseline NS5A polymorphisms: Elbasvir 50 mg/grazoprevir 100 mg once daily plus weight-based ribavirin twice daily [21]
(ELB/GRZ; Zepatier plus RBV; Copegus)
16 weeks
*Pegylated interferon plus ribavirin. 

 

Table 11. Genotype 1a • Prior failure with PEG-IFN plus RBV* • Compensated cirrhosis

Choose 1 of the following regimens for retreatment (AI):

Duration

Glecaprevir 300 mg/pibrentasvir 120 mg once daily [1,2]
(GLE/PIB; Mavyret)

12 weeks

Ledipasvir 90 mg/sofosbuvir 400 mg once daily [15,22]
(LED/SOF; Harvoni)

24 weeks

Ledipasvir 90 mg/sofosbuvir 400 mg once daily plus weight-based ribavirin twice daily [15,22]
(LED/SOF; Harvoni plus RBV; Copegus)

12 weeks

Paritaprevir 150 mg/ritonavir 100 mg/ombitasvir 25 mg/dasabuvir 600 mg once daily plus weight-based ribavirin twice daily [23]
(PTV/RTV/OBV/DSV; PrOD; Viekira XR plus RBV; Copegus)

24 weeks

Sofosbuvir 400 mg/velpatasvir 100 mg once daily [5]
(SOF/VEL; Epclusa)

12 weeks

Without baseline NS5A polymorphisms: Elbasvir 50 mg/grazoprevir 100 mg once daily [6]
(ELB/GRZ; Zepatier)

12 weeks
With baseline NS5A polymorphisms: Elbasvir 50 mg/grazoprevir 100 mg once daily plus weight-based ribavirin twice daily [9]
(ELB/GRZ; Zepatier plus RBV; Copegus)
16 weeks

*Pegylated interferon plus ribavirin.

References
  1. Kwo PY, Poordad F, Asatryan A, et al. Glecaprevir and pibrentasvir yield high response rates in patients with HCV genotype 1-6 without cirrhosis. J Hepatol 2017;67(2):263-71. [PMID: 28412293]
  2. U.S. Food and Drug Administration. Mavyret (glecaprevir/pibrentasvir). https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209394s000lbl.pdf [accessed 2017 Nov 30]
  3. Feld JJ, Kowdley KV, Coakley E, et al. Treatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. N Engl J Med 2014;370(17):1594-603. [PMID: 24720703]
  4. Ferenci P, Bernstein D, Lalezari J, et al. ABT-450/r-ombitasvir and dasabuvir with or without ribavirin for HCV. N Engl J Med 2014;370(21):1983-92. [PMID: 24795200]
  5. Feld JJ, Jacobson IM, Hezode C, et al. Sofosbuvir and velpatasvir for HCV genotype 1, 2, 4, 5, and 6 infection. N Engl J Med 2015;373(27):2599-607. [PMID: 26571066]
  6. Lawitz E, Gane E, Pearlman B, et al. Efficacy and safety of 12 weeks versus 18 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin for hepatitis C virus genotype 1 infection in previously untreated patients with cirrhosis and patients with previous null response with or without cirrhosis (C-WORTHY): a randomised, open-label phase 2 trial. Lancet 2015b;385(9973):1075-86. [PMID: 25467591]
  7. Sulkowski M, Hezode C, Gerstoft J, et al. Efficacy and safety of 8 weeks versus 12 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin in patients with hepatitis C virus genotype 1 mono-infection and HIV/hepatitis C virus co-infection (C-WORTHY): a randomised, open-label phase 2 trial. Lancet 2015;385(9973):1087-97. [PMID: 25467560]
  8. Zeuzem S, Ghalib R, Reddy KR, et al. Grazoprevir-elbasvir combination therapy for treatment-naive cirrhotic and noncirrhotic patients with chronic hepatitis C virus genotype 1, 4, or 6 infection: a randomized trial. Ann Intern Med 2015;163(1):1-13. [PMID: 25909356]
  9. U.S. Food and Drug Administration. Zepatier (elbasvir/grazoprevir). http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208261Orig1s000lbl.pdf [accessed 2017 Nov 30]
  10. Kowdley KV, Gordon SC, Reddy KR, et al. Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. N Engl J Med 2014;370(20):1879-88. [PMID: 24720702]
  11. Kowdley KV, Sundaram V, Jeon CY, et al. Eight weeks of ledipasvir/sofosbuvir is effective for selected patients with genotype 1 hepatitis C virus infection. Hepatology 2017;65(4):1094-103. [PMID: 28027579]
  12. Terrault NA, Zeuzem S, Di Bisceglie AM, et al. Effectiveness of Ledipasvir-Sofosbuvir Combination in Patients With Hepatitis C Virus Infection and Factors Associated With Sustained Virologic Response. Gastroenterology 2016;151(6):1131-40.e5.
  13. U.S. Food and Drug Administration. Harvoni (ledipasvir/sofosbuvir). 2015. https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/205834s001lbl.pdf [accessed 2017 Dec 13]
  14. Gane E, Poordad F, Wang S, et al. High Efficacy of ABT-493 and ABT-530 Treatment in Patients With HCV Genotype 1 or 3 Infection and Compensated Cirrhosis. Gastroenterology 2016;151(4):651-59.e1. [PMID: 27456384]
  15. Bourliere M, Bronowicki JP, de Ledinghen V, et al. Ledipasvir-sofosbuvir with or without ribavirin to treat patients with HCV genotype 1 infection and cirrhosis non-responsive to previous protease-inhibitor therapy: a randomised, double-blind, phase 2 trial (SIRIUS). Lancet Infect Dis 2015;15(4):397-404. [PMID: 25773757]
  16. Reddy KR, Bourliere M, Sulkowski M, et al. Ledipasvir and sofosbuvir in patients with genotype 1 hepatitis C virus infection and compensated cirrhosis: An integrated safety and efficacy analysis. Hepatology 2015;62(1):79-86. [PMID: 25846144]
  17. U.S. Food and Drug Administration. Viekira XR (dasabuvir, ombitasvir, paritaprevir, and ritonavir tablets), Copackaged for Oral Use. 2.  https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208624s001s003lbl.pdf [accessed March 7, 2017]
  18. Afdhal N, Reddy KR, Nelson DR, et al. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med 2014;370(16):1483-93. [PMID: 24725238]
  19. Zeuzem S, Jacobson IM, Baykal T, et al. Retreatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. N Engl J Med 2014;370(17):1604-14. [PMID: 24720679]
  20. Forns X, Gordon SC, Zuckerman E, et al. Grazoprevir and elbasvir plus ribavirin for chronic HCV genotype-1 infection after failure of combination therapy containing a direct-acting antiviral agent. J Hepatol 2015;63(3):564-72. [PMID: 25895428]
  21. Buti M, Gordon SC, Zuckerman E, et al. Grazoprevir, Elbasvir, and Ribavirin for Chronic Hepatitis C Virus Genotype 1 Infection After Failure of Pegylated Interferon and Ribavirin With an Earlier-Generation Protease Inhibitor: Final 24-Week Results From C-SALVAGE. Clin Infect Dis 2016;62(1):32-6. [PMID: 26371152]
  22. Bourliere M OM, et al, editor An integrated safety and efficacy analysis of >500 patients with compensated cirrhosis treated with ledipasvir/sofosbuvir with or without ribavirin. 65th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD); 2014; Boston, MA.
  23. Poordad F, Hezode C, Trinh R, et al. ABT-450/r-ombitasvir and dasabuvir with ribavirin for hepatitis C with cirrhosis. N Engl J Med 2014;370(21):1973-82. [PMID: 24725237]

Genotype 1b

Hepatitis C Virus Infection Guideline Committee, December 2017

RECOMMENDATIONS
  • Based on the results of the pretreatment assessment, clinicians should choose from among the treatment regimens for patients with hepatitis C virus (HCV) genotype 1b listed in tables 12 through 15, below.
  • If a regimen with weight-based ribavirin (RBV) is chosen, clinicians should dose as follows: (AI)
    • <75 kg: RBV 400 mg once daily + 600 mg once daily (total daily dose: 1000 mg)
    • ≥75 kg: RBV 600 mg twice daily (total daily dose: 1200 mg)

The regimens listed in tables 12 through 15, below, are recommended for patients with HCV genotype 1b. All drugs in the recommended regimens are oral medications. Multiple factors influence the choice of regimen, including, but not limited to, the patient’s treatment status (naive or previous HCV treatment failure), the presence of cirrhosis, preferences, and all previously noted considerations.

Drug names: Use of a “/” between two drug names indicates a co-formulated tablet. Use of the word “plus” indicates two separate drugs.

Rating of regimens: All regimen choices listed are rated AI (strong recommendation, with high-quality evidence from at least 1 randomized trial with clinical outcomes and/or validated laboratory endpoints) except where indicated. 

Table 12. Genotype 1b • Treatment-naive • No cirrhosis

Choose 1 of the following regimens (AI):

Duration

Elbasvir 50 mg/grazoprevir 100 mg once daily [1-3]
(ELB/GRZ; Zepatier)

12 weeks

Glecaprevir 300 mg/pibrentasvir 120 mg once daily [4,5]
(GLE/PIB; Mavyret)

8 weeks

Paritaprevir 150 mg/ritonavir 100 mg/ombitasvir 25 mg/dasabuvir 600 mg once daily [6,7]
(PTV/RTV/OBV/DSV; PrOD; Viekira XR)

12 weeks

Sofosbuvir 400 mg/velpatasvir 100 mg once daily [8]
(SOF/VEL; Epclusa)

12 weeks

For patients who are non-black, HIV-uninfected, and have HCV RNA <6 million copies/mL (AII): Ledipasvir 90 mg/sofosbuvir 400 mg once daily [9-12]
(LED/SOF; Harvoni)  

8 weeks
For patients who are black, HIV-infected, or have HCV RNA ≥6 million copies/mL: Ledipasvir 90 mg/sofosbuvir 400 mg once daily [9-12]
(LED/SOF; Harvoni)
12 weeks

Table 13. Genotype 1b • Treatment-naive • Compensated cirrhosis

Choose 1 of the following regimens (AI):

Duration

Ledipasvir 90 mg/sofosbuvir 400 mg once daily [13,14]
(LED/SOF; Harvoni)

12 weeks

Elbasvir 50 mg/grazoprevir 100 mg once daily [1,2]
(ELB/GRZ; Zepatier)

12 weeks

Glecaprevir 300 mg/pibrentasvir 120 mg once daily [4]
(GLE/PIB; Mavyret)

12 weeks

Paritaprevir 150 mg/ritonavir 100 mg/ombitasvir 25 mg/dasabuvir 600 mg once daily [6]
(PTV/RTV/OBV/DSV; PrOD; Viekira XR)

12 weeks

Sofosbuvir 400 mg/velpatasvir 100 mg once daily [8]
(SOF/VEL; Epclusa)

12 weeks

Table 14. Genotype 1b • Prior failure with PEG-IFN plus RBV* • No cirrhosis

Choose 1 of the following regimens for retreatment (AI):

Duration

Elbasvir 50 mg/grazoprevir 100 mg once daily [2]
(ELB/GRZ; Zepatier)

12 weeks

Glecaprevir 300 mg/pibrentasvir 120 mg once daily [4,15]
(GLE/PIB; Mavyret)

8 weeks

Ledipasvir 90 mg/sofosbuvir 400 mg once daily [16,17]
(LED/SOF; Harvoni)

12 weeks

Paritaprevir 150 mg/ritonavir 100 mg/ombitasvir 25 mg/dasabuvir 600 mg once daily [18]
(PTV/RTV/OBV/DSV; PrOD; Viekira XR) 

12 weeks

Sofosbuvir 400 mg/velpatasvir 100 mg once daily [8]
(SOF/VEL; Epclusa)

12 weeks

*Pegylated interferon plus ribavirin.

Table 15. Genotype 1b • Prior failure with PEG-IFN plus RBV* • Compensated cirrhosis

Choose 1 of the following regimens for retreatment (AI):

Duration

Elbasvir 50 mg/grazoprevir 100 mg once daily [2]
(ELB/GRZ; Zepatier)

12 weeks

Glecaprevir 300 mg/pibrentasvir 120 mg once daily [4]
(GLE/PIB; Mavyret)

12 weeks

Ledipasvir 90 mg/sofosbuvir 400 mg once daily [13,19]
(LED/SOF; Harvoni)

24 weeks
Ledipasvir 90 mg/sofosbuvir 400 mg once daily plus weight-based ribavirin twice daily [13,19]
(LED/SOF; Harvoni plus RBV; Copegus)
12 weeks

Paritaprevir 150 mg/ritonavir 100 mg/ombitasvir 25 mg/dasabuvir 600 mg once daily [20
(PTV/RTV/OBV/DSV; PrOD; Viekira XR) 

12 weeks

Sofosbuvir 400 mg/velpatasvir 100 mg once daily [8]
(SOF/VEL; Epclusa)

12 weeks

*Pegylated interferon plus ribavirin.

References
  1. Zeuzem S, Ghalib R, Reddy KR, et al. Grazoprevir-elbasvir combination therapy for treatment-naive cirrhotic and noncirrhotic patients with chronic hepatitis C virus genotype 1, 4, or 6 infection: a randomized trial. Ann Intern Med 2015;163(1):1-13. [PMID: 25909356]
  2. Lawitz E, Gane E, Pearlman B, et al. Efficacy and safety of 12 weeks versus 18 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin for hepatitis C virus genotype 1 infection in previously untreated patients with cirrhosis and patients with previous null response with or without cirrhosis (C-WORTHY): a randomised, open-label phase 2 trial. Lancet 2015b;385(9973):1075-86. [PMID: 25467591]
  3. Sulkowski M, Hezode C, Gerstoft J, et al. Efficacy and safety of 8 weeks versus 12 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin in patients with hepatitis C virus genotype 1 mono-infection and HIV/hepatitis C virus co-infection (C-WORTHY): a randomised, open-label phase 2 trial. Lancet 2015;385(9973):1087-97. [PMID: 25467560]
  4. U.S. Food and Drug Administration. Mavyret (glecaprevir/pibrentasvir). https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209394s000lbl.pdf [accessed 2017 Nov 30]
  5. Kwo PY, Poordad F, Asatryan A, et al. Glecaprevir and pibrentasvir yield high response rates in patients with HCV genotype 1-6 without cirrhosis. J Hepatol 2017;67(2):263-71. [PMID: 28412293]
  6. Feld JJ, Kowdley KV, Coakley E, et al. Treatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. N Engl J Med 2014;370(17):1594-603. [PMID: 24720703]
  7. Ferenci P, Bernstein D, Lalezari J, et al. ABT-450/r-ombitasvir and dasabuvir with or without ribavirin for HCV. N Engl J Med 2014;370(21):1983-92. [PMID: 24795200]
  8. Feld JJ, Jacobson IM, Hezode C, et al. Sofosbuvir and velpatasvir for HCV genotype 1, 2, 4, 5, and 6 infection. N Engl J Med 2015;373(27):2599-607. [PMID: 26571066]
  9. Kowdley KV, Gordon SC, Reddy KR, et al. Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. N Engl J Med 2014;370(20):1879-88. [PMID: 24720702]
  10. Kowdley KV, Sundaram V, Jeon CY, et al. Eight weeks of ledipasvir/sofosbuvir is effective for selected patients with genotype 1 hepatitis C virus infection. Hepatology 2017;65(4):1094-103. [PMID: 28027579]
  11. Terrault NA, Zeuzem S, Di Bisceglie AM, et al. Effectiveness of Ledipasvir-Sofosbuvir Combination in Patients With Hepatitis C Virus Infection and Factors Associated With Sustained Virologic Response. Gastroenterology 2016;151(6):1131-40.e5.
  12. U.S. Food and Drug Administration. Harvoni (ledipasvir/sofosbuvir). 2015. https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/205834s001lbl.pdf [accessed 2017 Dec 13]
  13. Bourliere M, Bronowicki JP, de Ledinghen V, et al. Ledipasvir-sofosbuvir with or without ribavirin to treat patients with HCV genotype 1 infection and cirrhosis non-responsive to previous protease-inhibitor therapy: a randomised, double-blind, phase 2 trial (SIRIUS). Lancet Infect Dis 2015;15(4):397-404. [PMID: 25773757]
  14. Reddy KR, Bourliere M, Sulkowski M, et al. Ledipasvir and sofosbuvir in patients with genotype 1 hepatitis C virus infection and compensated cirrhosis: An integrated safety and efficacy analysis. Hepatology 2015;62(1):79-86. [PMID: 25846144]
  15. Poordad F, Felizarta F, Asatryan A, et al. Glecaprevir and pibrentasvir for 12 weeks for hepatitis C virus genotype 1 infection and prior direct-acting antiviral treatment. Hepatology 2017;66(2):389-97. [PMID: 28128852]
  16. Lawitz E, Poordad FF, Pang PS, et al. Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin in treatment-naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): an open-label, randomised, phase 2 trial. Lancet 2014a;383(9916):515-23. [PMID: 24209977]
  17. Afdhal N, Reddy KR, Nelson DR, et al. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med 2014;370(16):1483-93. [PMID: 24725238]
  18. Andreone P, Colombo MG, Enejosa JV, et al. ABT-450, ritonavir, ombitasvir, and dasabuvir achieves 97% and 100% sustained virologic response with or without ribavirin in treatment-experienced patients with HCV genotype 1b infection. Gastroenterology 2014;147(2):359-65.e1. [PMID: 24818763]
  19. Bourliere M OM, et al, editor An integrated safety and efficacy analysis of >500 patients with compensated cirrhosis treated with ledipasvir/sofosbuvir with or without ribavirin. 65th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD); 2014; Boston, MA.
  20. Poordad F, Hezode C, Trinh R, et al. ABT-450/r-ombitasvir and dasabuvir with ribavirin for hepatitis C with cirrhosis. N Engl J Med 2014;370(21):1973-82. [PMID: 24725237]

Genotype 2

Hepatitis C Virus Infection Guideline Committee, December 2017

Recommendation
  • Based on the results of the pretreatment assessment, clinicians should choose from among the treatment regimens for patients with hepatitis C virus (HCV) genotype 2 listed in tables 16 through 18, below.

The regimens listed tables 16 through 18, below, are recommended for patients with HCV genotype 2. All drugs in the recommended regimens are oral medications. Factors that determine choice of regimen include the patient’s treatment status (naive or previous HCV treatment failure), the presence of cirrhosis, preferences, and all previously noted considerations.

Drug names: Use of a “/” between two drug names indicates a co-formulated tablet. Use of the word “plus” indicates two separate drugs.

Note: The daclatasvir plus sofosbuvir regimen is not approved by the U.S. Food and Drug Administration for treatment of patients with genotype 2 HCV infection as of March 31, 2017; however, published evidence [1] supports use of this combination, and it is commonly prescribed.

Table 16. Genotype 2 • Treatment-naive • No cirrhosis

Choose 1 of the following regimens (AI):

Duration

Glecaprevir 300 mg/pibrentasvir 120 mg once daily [1,2] 
(GLE/PIB; Mavyret)

8 weeks

Sofosbuvir 400 mg/velpatasvir 100 mg once daily [3]
(SOF/VEL; Epclusa)

12 weeks

 

Table 17. Genotype 2 • Treatment-naive • Compensated cirrhosis

Choose 1 of the following regimens (AI):

Duration

Glecaprevir 300 mg/pibrentasvir 120 mg once daily [2] 
(GLE/PIB; Mavyret)

12 weeks

Sofosbuvir 400 mg/velpatasvir 100 mg once daily [3]
(SOF/VEL; Epclusa)

12 weeks

 

Table 18. Genotype 2 • Prior failure with PEG-IFN plus RBV* • No cirrhosis OR compensated cirrhosis

Choose 1 of the following regimens for retreatment (AI):

Duration

No cirrhosis: Glecaprevir 300 mg/pibrentasvir 120 mg once daily [1,2] 
(GLE/PIB; Mavyret)

8 weeks 

Compensated cirrhosis: Glecaprevir 300 mg/pibrentasvir 120 mg once daily [1,2] 
(GLE/PIB; Mavyret)

12 weeks

Sofosbuvir 400 mg/velpatasvir 100 mg once daily [3] 
(SOF/VEL; Epclusa) 

12 weeks

*Pegylated interferon plus ribavirin.

 References

  1. Kwo PY, Poordad F, Asatryan A, et al. Glecaprevir and pibrentasvir yield high response rates in patients with HCV genotype 1-6 without cirrhosis. J Hepatol 2017;67(2):263-71. [PMID: 28412293]
  2. U.S. Food and Drug Administration. Mavyret (glecaprevir/pibrentasvir). https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209394s000lbl.pdf [accessed 2017 Nov 30]
  3. Foster GR, Afdhal N, Roberts SK, et al. Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection. N Engl J Med 2015;373(27):2608-17. [PMID: 26575258]

Genotype 3

Hepatitis C Virus Infection Guideline Committee, December 2017

RECOMMENDATION
  • Based on the results of the pretreatment assessment, clinicians should choose from among the treatment regimens for patients with hepatitis C virus (HCV) genotype 3 listed in tables 19 through 22, below.

The regimens listed in tables 19 through 22, below, are recommended for patients with HCV genotype 3. All drugs in the recommended regimens are oral medications. Factors that determine choice of regimen include the patient’s treatment status (naive or previous HCV treatment failure), the presence of cirrhosis, preferences, and all previously noted considerations.

Drug names: Use of a “/” between two drug names indicates a co-formulated tablet. Use of the word “plus” indicates two separate drugs.

Sustained virologic response (SVR) rate: SVR rates are listed from studies of patients with HCV genotype 3 (reference numbers are cited in each table). These data have been included only for genotype 3 because, to date, achievement of an SVR in these patients, especially those with cirrhosis, has proven to be more difficult than it is in patients with other HCV genotypes.

Table 19.  Genotype 3 • Treatment-naive • No cirrhosis

Choose 1 of the following regimens (AI):

Duration

Glecaprevir 300 mg/pibrentasvir 120 mg once daily (SVR, 83% to 94%) [1,2]
(GLE/PIB; Mavyret)

8 weeks

Sofosbuvir 400/velpatasvir 100 mg once daily (SVR, 98%) [3]
(SOF/VEL; Epclusa)

12 weeks

 

Table 20. Genotype 3 • Treatment-naive • Compensated cirrhosis

Choose 1 of the following regimens (AI):

Duration

Glecaprevir 300 mg/pibrentasvir 120 mg once daily (SVR, 98%) [1]
(GLE/PIB; Mavyret)

12 weeks

Sofosbuvir 400 mg/velpatasvir 100 mg once daily (SVR, 93%) [3]
(SOF/VEL; Epclusa)

12 weeks

 

Table 21. Genotype 3 • Prior failure with Peg-IFN plus RBV* • No cirrhosis

Choose 1 of the following regimens for retreatment (AI):

Duration

Glecaprevir 300 mg/pibrentasvir 120 mg once daily (SVR, 98%) [1]
(GLE/PIB; Mavyret)

16 weeks

Sofosbuvir 400 mg/velpatasvir 100 mg once daily (SVR, 91%) [3]
(SOF/VEL; Epclusa)

12 weeks

*Pegylated interferon plus ribavirin.

 

Table 22. Genotype 3 • Prior failure with PEG-IFN plus RBV* • Compensated cirrhosis

Choose 1 of the following regimens for retreatment (AI):

Duration

Glecaprevir 300 mg/pibrentasvir 120 mg once daily (SVR, 98%) [1]
(SOF/VEL; Epclusa)

16 weeks

Sofosbuvir 400 mg/velpatasvir 100 mg once daily (SVR, 89%) [4]
(SOF/VEL; Epclusa)

12 weeks

*Pegylated interferon plus ribavirin.

References
  1. U.S. Food and Drug Administration. Mavyret (glecaprevir/pibrentasvir). https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209394s000lbl.pdf [accessed 2017 Nov 30]
  2. Kwo PY, Poordad F, Asatryan A, et al. Glecaprevir and pibrentasvir yield high response rates in patients with HCV genotype 1-6 without cirrhosis. J Hepatol 2017;67(2):263-71. [PMID: 28412293]
  3. Foster GR, Pianko S, Brown A, et al. Efficacy of sofosbuvir plus ribavirin with or without peginterferon-alfa in patients with hepatitis C virus genotype 3 infection and treatment-experienced patients with cirrhosis and hepatitis C virus genotype 2 infection. Gastroenterology 2015;149(6):1462-70. [PMID: 26248087]
  4. Foster GR, Afdhal N, Roberts SK, et al. Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection. N Engl J Med 2015;373(27):2608-17. [PMID: 26575258]

Genotype 4

Hepatitis C Virus Infection Guideline Committee, December 2017

RECOMMENDATIONS
  • Based on the results of the pretreatment assessment, clinicians should choose from among the treatment regimens for patients with hepatitis C virus (HCV) genotype 4 listed in tables 23 and 24, below.
  • If a regimen with weight-based ribavirin (RBV) is chosen, clinicians should dose as follows: (AI)
    • <75 kg: RBV 400 mg once daily + 600 mg once daily (total daily dose: 1000 mg)
    • ≥75 kg: RBV 600 mg twice daily (total daily dose: 1200 mg)

The regimens listed in tables 23 and 24, below, are recommended for patients with HCV genotype 4. All drugs in the recommended regimens are oral medications. Factors that determine choice of regimen include the patient’s treatment status (naive or previous HCV treatment failure), preferences, and all limitations noted in the Considerations section of this guideline.

Drug names: Use of a “/” between two drug names indicates a co-formulated tablet. Use of the word “plus” indicates two separate drugs.

Table 23. Genotype 4 • Treatment-naive • No cirrhosis OR compensated cirrhosis

Choose 1 of the following regimens (AI):

Duration

Elbasvir 50 mg/grazoprevir 100 mg once daily [1]
(ELB/GRZ; Zepatier)

12 weeks

No cirrhosis: Glecaprevir 300 mg/pibrentasvir 120 mg once daily [2,3]
(GLE/PIB; Mavyret)

8 weeks

Compensated cirrhosis: Glecaprevir 300 mg/pibrentasvir 120 mg once daily [2,3]
(GLE/PIB; Mavyret)

12 weeks

Ledipasvir 90 mg/sofosbuvir 400 mg once daily [4,5]
(LED/SOF; Harvoni)

12 weeks

Paritaprevir 150 mg/ritonavir 100 mg/ombitasvir 25 mg once daily plus weight-based ribavirin twice daily [6]
(PTV/RTV/OBV; Technivie plus RBV; Copegus)

12 weeks

Sofosbuvir 400 mg/velpatasvir 100 mg once daily [7]
(SOF/VEL; Epclusa)

12 weeks

 

Table 24. Genotype 4 • Prior failure with Peg-IFN plus RBV* • No cirrhosis OR compensated cirrhosis

Choose 1 of the following regimens for retreatment (AI):

Duration

No cirrhosis: Elbasvir 50 mg/grazoprevir 100 mg once daily plus weight-based ribavirin twice daily [1,8]
(ELB/GRZ; Zepatier plus RBV; Copegus)

12 weeks

Compensated cirrhosis: Elbasvir 50 mg/grazoprevir 100 mg once daily plus weight-based ribavirin twice daily [1,8]
(ELB/GRZ; Zepatier plsu RBV; Copegus)

16 weeks

No cirrhosis: Glecaprevir 300 mg/pibrentasvir 120 mg once daily [2,3]
(GLE/PIB; Mavyret)

8 weeks

Compensated cirrhosis: Glecaprevir 300 mg/pibrentasvir 120 mg once daily [2,3]
(GLE/PIB; Mavyret)

12 weeks

Ledipasvir 90 mg/sofosbuvir 400 mg once daily [4]
(LED/SOF; Harvoni)

12 weeks

Paritaprevir 150 mg/ritonavir 100 mg/ombitasvir 25 mg once daily plus weight-based ribavirin twice daily [6]
(PTV/RTV/OBV; Technivie plus RBV; Copegus)

12 weeks

Sofosbuvir 400 mg/velpatasvir 100 mg once daily [7]
(SOF/VEL; Epclusa)

12 weeks

*Pegylated interferon plus ribavirin.

References

  1. Zeuzem S, Ghalib R, Reddy KR, et al. Grazoprevir-elbasvir combination therapy for treatment-naive cirrhotic and noncirrhotic patients with chronic hepatitis C virus genotype 1, 4, or 6 infection: a randomized trial. Ann Intern Med 2015;163(1):1-13. [PMID: 25909356]
  2. U.S. Food and Drug Administration. Mavyret (glecaprevir/pibrentasvir). https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209394s000lbl.pdf [accessed 2017 Nov 30]
  3. Kwo PY, Poordad F, Asatryan A, et al. Glecaprevir and pibrentasvir yield high response rates in patients with HCV genotype 1-6 without cirrhosis. J Hepatol 2017;67(2):263-71. [PMID: 28412293]
  4. Kohli A, Kapoor R, Sims Z, et al. Ledipasvir and sofosbuvir for hepatitis C genotype 4: a proof-of-concept, single-centre, open-label phase 2a cohort study. Lancet Infect Dis 2015;15(9):1049-54. [PMID: 26187031]
  5. Abergel A, Asselah T, Metivier S, et al. Ledipasvir-sofosbuvir in patients with hepatitis C virus genotype 5 infection: an open-label, multicentre, single-arm, phase 2 study. Lancet Infect Dis 2016;16(4):459-64. [PMID: 26803446]
  6. Hezode C, Asselah T, Reddy KR, et al. Ombitasvir plus paritaprevir plus ritonavir with or without ribavirin in treatment-naive and treatment-experienced patients with genotype 4 chronic hepatitis C virus infection (PEARL-I): a randomised, open-label trial. Lancet 2015;385(9986):2502-9. [PMID: 25837829]
  7. Feld JJ, Jacobson IM, Hezode C, et al. Sofosbuvir and velpatasvir for HCV genotype 1, 2, 4, 5, and 6 infection. N Engl J Med 2015;373(27):2599-607. [PMID: 26571066]
  8. U.S. Food and Drug Administration. Zepatier (elbasvir/grazoprevir). http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208261Orig1s000lbl.pdf [accessed 2017 Nov 30]

Genotype 5

Hepatitis C Virus Infection Guideline Committee, December 2017

RECOMMENDATION
  • Based on the results of the pretreatment assessment, clinicians should choose from among the treatment regimens for patients with hepatitis C virus (HCV) genotype 5 listed in tables 25 and 26, below.

The regimens listed in tables 25 and 26, below, are recommended for patients with HCV genotype 5. All drugs in the recommended regimens are oral medications. Factors that determine the choice of regimen include the patient’s treatment status (naive or previous HCV treatment failure) and preferences.

Drug names: Use of a “/” between two drug names indicates a co-formulated tablet. Use of the word “plus” indicates two separate drugs.

Table 25. Genotype 5 • Treatment-naive • No cirrhosis OR compensated cirrhosis

Choose 1 of the following regimens (AI):

Duration

No cirrhosis: Glecaprevir 300 mg/pibrentasvir 120 mg once daily [1,2]
(GLE/PIB; Mavyret)

8 weeks

Compensated cirrhosis: Glecaprevir 300 mg/pibrentasvir 120 mg once daily [1,2]
(GLE/PIB; Mavyret)

12 weeks

Ledipasvir 90 mg/sofosbuvir 400 mg once daily [3]
(LED/SOF; Harvoni)

12 weeks

Sofosbuvir 400 mg/velpatasvir 100 mg once daily [4]
(SOF/VEL; Epclusa)

12 weeks

 

Table 26. Genotype 5 • Prior failure with PEG-IFN plus RBV* • No cirrhosis OR compensated cirrhosis

Choose 1 of the following regimens for retreatment (AI):

Duration

No cirrhosis: Glecaprevir 300 mg/pibrentasvir 120 mg once daily [1,2]
(GLE/PIB; Mavyret)

8 weeks

Compensated cirrhosis: Glecaprevir 300 mg/pibrentasvir 120 mg once daily [1,2]
(GLE/PIB; Mavyret)

12 weeks

Ledipasvir 90 mg/sofosbuvir 400 mg once daily [3]
(LED/SOF; Harvoni)

12 weeks

Sofosbuvir 400 mg/velpatasvir 100 mg once daily [4]
(SOF/VEL; Epclusa)

12 weeks

*Pegylated interferon plus ribavirin.

References
  1. Kwo PY, Poordad F, Asatryan A, et al. Glecaprevir and pibrentasvir yield high response rates in patients with HCV genotype 1-6 without cirrhosis. J Hepatol 2017;67(2):263-71. [PMID: 28412293]
  2. U.S. Food and Drug Administration. Mavyret (glecaprevir/pibrentasvir). https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209394s000lbl.pdf [accessed 2017 Nov 30]
  3. Abergel A, Asselah T, Metivier S, et al. Ledipasvir-sofosbuvir in patients with hepatitis C virus genotype 5 infection: an open-label, multicentre, single-arm, phase 2 study. Lancet Infect Dis 2016;16(4):459-64. [PMID: 26803446]
  4. Feld JJ, Jacobson IM, Hezode C, et al. Sofosbuvir and velpatasvir for HCV genotype 1, 2, 4, 5, and 6 infection. N Engl J Med 2015;373(27):2599-607. [PMID: 26571066]

Genotype 6

Hepatitis C Virus Infection Guideline Committee, December 2017

RECOMMENDATION
  • Based on the results of the pretreatment assessment, clinicians should choose from among the treatment regimens for patients with hepatitis C virus (HCV) genotype 6 listed in tables 27 and 28, below.

The regimens listed in tables 27 and 28, below, are recommended for patients with HCV genotype 6. All drugs in the recommended regimens are oral medications. Factors that determine the choice of regimen include the patient’s treatment status (naive or previous HCV treatment failure) and preferences.

Drug names: Use of a “/” between two drug names indicates a co-formulated tablet. Use of the word “plus” indicates two separate drugs.

Table 27. Genotype 6 • Treatment-naive • No cirrhosis OR compensated cirrhosis

Choose 1 of the following regimens (AI):

Duration

No cirrhosis: Glecaprevir 300 mg/pibrentasvir 120 mg once daily [1,2]
(GLE/PIB; Mavyret)

8 weeks

Compensated cirrhosis: Glecaprevir 300 mg/pibrentasvir 120 mg once daily [1,2]
(GLE/PIB; Mavyret)

12 weeks

Ledipasvir 90 mg/sofosbuvir 400 mg once daily [3]
(LED/SOF; Harvoni)

12 weeks

Sofosbuvir 400 mg/velpatasvir 100 mg once daily [4]
(SOF/VEL; Epclusa)

12 weeks

 

Table 28. Genotype 6 • Prior failure with PEG-IFN plus RBV* • No cirrhosis OR compensated cirrhosis

Choose 1 of the following regimens for retreatment (AI):

Duration

No cirrhosis: Glecaprevir 300 mg/pibrentasvir 120 mg once daily [1,2]
(GLE/PIB; Mavyret)

8 weeks

Compensated cirrhosis: Glecaprevir 300 mg/pibrentasvir 120 mg once daily [1,2]
(GLE/PIB; Mavyret)

12 weeks

Ledipasvir 90 mg/sofosbuvir 400 mg once daily [3]
(LED/SOF; Harvoni)

12 weeks

Sofosbuvir 400 mg/velpatasvir 100 mg once daily [4]
(SOF/VEL; Epclusa) 

12 weeks

*Pegylated interferon plus ribavirin.

References
  1. U.S. Food and Drug Administration. Mavyret (glecaprevir/pibrentasvir). https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209394s000lbl.pdf [accessed 2017 Nov 30]
  2. Kwo PY, Poordad F, Asatryan A, et al. Glecaprevir and pibrentasvir yield high response rates in patients with HCV genotype 1-6 without cirrhosis. J Hepatol 2017;67(2):263-71. [PMID: 28412293]
  3. Gane EJ, Hyland RH, An D, et al. Efficacy of ledipasvir and sofosbuvir, with or without ribavirin, for 12 weeks in patients with HCV genotype 3 or 6 infection. Gastroenterology 2015;149(6):1454-61.e1. [PMID: 26261007]
  4. Feld JJ, Jacobson IM, Hezode C, et al. Sofosbuvir and velpatasvir for HCV genotype 1, 2, 4, 5, and 6 infection. N Engl J Med 2015;373(27):2599-607. [PMID: 26571066]